Chemoprevention of bilirubin encephalopathy with a nanoceutical agent.

BACKGROUND: Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. We investigated a novel spinel-structured citrate-functionalized trimanganese tetroxide nanoparticle (C-Mn3O4 NP, the nanodrug) to degrade both systemic and neural bilirubin loads. METHOD: Severe neonatal unconjugated hyperbilirubinemia (SNH) was induced in neonatal C57BL/6j mice model with phenylhydrazine (PHz) intoxication. Efficiency of the nanodrug on both in vivo bilirubin degradation and amelioration of bilirubin encephalopathy and associated neurobehavioral sequelae were evaluated. RESULTS: Single oral dose (0.25 mg kg-1 bodyweight) of the nanodrug reduced both total serum bilirubin (TSB) and unconjugated bilirubin (UCB) in SNH rodents. Significant (p < 0.0001) UCB and TSB-degradation rates were reported within 4-8 h at 1.84 ± 0.26 and 2.19 ± 0.31 mg dL-1 h-1, respectively. Neural bilirubin load was decreased by 5.6 nmol g-1 (p = 0.0002) along with improved measures of neurobehavior, neuromotor movements, learning, and memory. Histopathological studies confirm that the nanodrug prevented neural cell reduction in Purkinje and substantia nigra regions, eosinophilic neurons, spongiosis, and cell shrinkage in SNH brain parenchyma. Brain oxidative status was maintained in nanodrug-treated SNH cohort. Pharmacokinetic data corroborated the bilirubin degradation rate with plasma nanodrug concentrations. CONCLUSION: This study demonstrates the in vivo capacity of this novel nanodrug to reduce systemic and neural bilirubin load and reverse bilirubin-induced neurotoxicity. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemopreventive approach to clinical settings. IMPACT: None of the current pharmacotherapeutics treat severe neonatal hyperbilirubinemia (SNH) to prevent risks of neurotoxicity. In this preclinical study, a newly investigated nano-formulation, citrate-functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs), exhibits bilirubin reduction properties in rodents. Chemopreventive properties of this nano-formulation demonstrate an efficacious, efficient agent that appears to be safe in these early studies. Translation of C-Mn3O4 NPs to prospective preclinical and clinical trials in appropriate in vivo models should be explored as a potential novel pharmacotherapy for SNH.

Bandwidth Enhancement of a V-Band Klystron with Stagger-Tuned Multiple Radial Re-Entrant Cavities.

The V-band frequencies are becoming popular due to their application potential towards secure high data rate communications. This article reports bandwidth enhancement of an 11-cavity V-band Klystron amplifier employing staggered tuning. A systematic approach is presented to stagger-tune the periodically allocated multiple cavities of the Klystron operating at 60.1 GHz. Using the three-dimensional particle-in-cell (PIC) simulation, it is shown that, employing the proposed approach, the -3 dB bandwidth of the device (with peak tuned configuration) has been increased from 165 MHz to 540 MHz, demonstrating a 260% increment. The -1 dB bandwidth of the device is estimated to be 270 MHz. The proposed approach of stagger tuning may be employed for similar devices employing multiple RF cavities to meet the requirement of wide bandwidth.

Host-Assisted Delivery of a Model Drug to Genomic DNA: Key Information from Ultrafast Spectroscopy and in silico Study.

Drug delivery to a target without adverse effects is one of the major criteria for clinical use. Herein, we have made an attempt to explore the delivery efficacy of SDS surfactant in a monomer and micellar stage during the delivery of the model drug, Toluidine Blue (TB) from the micellar cavity to DNA. Molecular recognition of pre-micellar SDS encapsulated TB with DNA occurs at a rate constant of k1 ∼652 s-1 . However, no significant release of encapsulated TB at micellar concentration was observed within the experimental time frame. This originated from the higher binding affinity of TB towards the nano-cavity of SDS at micellar concentration which does not allow the delivery of TB from the nano-cavity of SDS micelles to DNA. Thus, molecular recognition controls the extent of DNA recognition by TB which in turn modulates the rate of delivery of TB from SDS in a concentration-dependent manner.

A national survey on the management of foot drop secondary to lumbar degenerative disease in the United Kingdom.

PURPOSE: There is considerable variation in the management of foot drop secondary to lumbar degenerative disease (LDD) that occurs between centres and surgeons (spinal surgeons and neurosurgeons). The lack of standardised practice reflects the paucity in evidence base for management of this condition. In this survey, we aimed to assess current practice in the UK and identify the areas of variation. METHODS: A case-based survey was distributed to members of the Society of British Neurological Surgeons and British Association of Spine Surgeons through an online questionnaire. The survey consisted of 10 questions designed to determine the management of foot drop secondary to LDD. RESULTS: A total of 163 responses were collected among UK neurosurgeons and spinal surgeons with good geographical representation. 92% were Consultants. 86% of the respondents would offer surgery. The indication for offering surgery varied but 54% of respondents would offer surgery to patients who present with a painful foot drop. There was a huge variation in offering surgery dependent on the grade of weakness. The strongest prognostic indicator predicted was duration of weakness (92%). The timing of intervention was wide-ranging in the responses received. Almost all responded that they would be willing to participate in a prospective study in the future to determine best practice. CONCLUSIONS: This survey highlights the significant variability in management of foot drop secondary to LDD amongst consultant surgeons within the UK. It is also suggestive of a weak evidence base and indicates an urgent need for a high quality national prospective study.

Chemical Synthesis of ß-l-Rhamnose Containing the Pentasaccharide Repeating Unit of the O-Specific Polysaccharide from a Halophilic Bacterium Halomonas ventosae RU5S2EL in the Form of Its 2-Aminoethyl Glycoside.

Total synthesis of the pentasaccharide repeating unit of the OPS from Halomonas ventosae RU5S2EL is accomplished through a [3+2] block strategy. Picoloyl-induced hydrogen-bond-assisted aglycon delivery (HAD) is used for two consecutive 1,2-cis-l-rhamnosylations, and remote participation is used for α-selective glucosylation. The choice of 2-aminoethyl glycoside at the reducing end is opted for, leaving the scope for further glycoconjugate formation without hampering the reducing-end stereochemistry.

Prognostic indicators of surgical outcome in painful foot drop: a systematic review and meta-analysis.

PURPOSE: Foot drop is a relatively uncommon presentation of lumbar degenerative disease and there is currently a paucity of evidence on management and outcomes which is reflective of the lack of standardised treatment provided to patients. The purpose of this systematic review and meta-analysis is to determine the effectiveness of surgical management and the factors that predict surgical outcome. METHODS: A systematic database search of Cochrane Library, Ovid Medline, Pubmed, Embase and Google Scholar was undertaken from inception through August 2018. Only studies reporting on surgical outcome in adult patients who had a painful foot drop and underwent decompression were included. Case reports and studies with surgical fixation were excluded. Study quality was assessed using the Newcastle-Ottawa Scale. Data were pooled using a random-effects model. RESULTS: 797 studies were screened and 9 observational studies met the inclusion criteria. This resulted in a total of 431 patients who underwent decompression for foot drop. Pooled rates of outcome for improvement in foot drop MRC grade were 84.5% (range 67.9-96%). Sub-group meta-analyses of studies revealed a statistically significant association between duration of foot drop (pooled 4.95 [95% CI 1.13-21.74]), severity of preoperative weakness (pooled 0.38 [95% CI 0.15-0.93]) on post-operative outcome and age (pooled 6.28 [1.33-29.72]). CONCLUSION: This is the first systematic review and meta-analysis to explore the outcome and prognostic indicators of lumbar decompression for foot drop. Findings indicate that age, duration of foot drop weakness and MRC grade of foot drop prior to intervention were strong predictors of surgical outcome.

Intramedullary spinal cord tumours - a single Centre, 10-year review of clinical and pathological outcomes.

BACKGROUND: Intramedullary spinal cord tumours are relatively rare tumours of the central nervous system. Surgical outcomes are affected by many variables, including pre-operative neurological function, tumour histology and extent of resection. Emphasis remains on surgical treatment due to limited adjunctive therapeutic options and poor drug penetration. OBJECTIVE: To identify clinically relevant predictors of progression free survival by retrospectively analysing the extent of resection, pre- and post-operative neurological function and histology in intramedullary spinal cord tumours from a single neurosurgical centre over 10 years. METHODS: Forty-three adult cases were identified from a surgical database. Variables collected included pre-and post-operative Frankel Grade and Modified McCormick Scale assessments, tumour histology, extent of resection and length of follow up. Chi-Squared, Kaplan-Mier Survival and Mann-Whitney U-tests were completed. RESULTS: Ependymoma (41.9%) and haemangioblastoma (14.0%) were the commonest tumour histologies. In total, 17 different histological tumours were identified in the series. There was a statistically significant relationship between identification of the tumour plane and extent of resection (p < 0.01), along with the extent of resection and recurrence (p = 0.04). Compared to the other histological subtypes, ependymoma's demonstrated a significantly greater extent of resection (p = 0.01). There was a significant relationship between the grade of tumour and progression-free survival (p < 0.01). CONCLUSION: Tumour plane and the extent of tumour resection are significant determinants of progression-free survival. Ependymoma, whilst being the commonest histology in our series were also the most resectable. Whilst complete resection reduces the rate of recurrence, tumour grade is the most important predictor of outcome. Given the importance of the extent of resection, and following a similar trend to other low volume pathologies, these tumours should only be tackled by neurosurgeons with experience in their resection.

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside.

The total chemical synthesis of the pentasaccharide repeating unit of the O-polysaccharide from E. coli O132 is accomplished in the form of its 2-aminoethyl glycoside. The 2-aminoethyl glycoside is particularly important as it allows further glycoconjugate formation utilizing the terminal amine without affecting the stereochemistry of the reducing end. The target was achieved through a [3 + 2] strategy where the required monosaccharide building blocks are prepared from commercially available sugars through rational protecting group manipulation. The NIS-mediated activation of thioglycosides was used extensively for the glycosylation reactions throughout.

Targeted Redox Balancing through Pulmonary Nanomedicine Delivery Reverses Oxidative Stress Induced Lung Inflammation.

Non-invasive delivery of drugs is important for the reversal of respiratory diseases essentially by-passing metabolic pathways and targeting large surface area of drug absorption. Here, we study the inhalation of a redox nano medicine namely citrate functionalized Mn3O4 (C-Mn3O4) duly encapsulated in droplet evaporated aerosols for the balancing of oxidative stress generated by the exposure of Chromium (VI) ion, a potential lung carcinogenic agent. Our optical spectroscopic in-vitro experiments demonstrates the efficacy of redox balancing of the encapsulated nanoparticles (NP) for the maintenance of a homeostatic condition. The formation of Cr-NP complex as an excretion of the heavy metal is also demonstrated through optical spectroscopic and high resolution transmission optical microscopy (HRTEM). Our studies confirm the oxidative stress mitigation activity of the Cr-NP complex. A detailed immunological assay followed by histopathological studies and assessment of mitochondrial parameters in pre-clinical mice model with chromium (Cr) induced lung inflammation establishes the mechanism of drug action to be redox-buffering. Thus, localised delivery of C-Mn3O4 NPs in the respiratory tract via aerosols can act as an effective nanotherapeutic agent against oxidative stress induced lung inflammation.

A study of scarless wound healing through programmed inflammation, proliferation and maturation using a redox balancing nanogel.

In the study, we have shown the efficacy of an indigenously developed redox balancing chitosan gel with impregnated citrate capped Mn3O4 nanoparticles (nanogel). Application of the nanogel on a wound of preclinical mice model shows role of various signaling molecules and growth factors, and involvement of reactive oxygen species (ROS) at every stage, namely hemostasis, inflammation, and proliferation leading to complete maturation for the scarless wound healing. While in vitro characterization of nanogel using SEM, EDAX, and optical spectroscopy reveals pH regulated redox buffering capacity, in vivo preclinical studies on Swiss albino involving IL-12, IFN-γ, and α-SMA signaling molecules and detailed histopathological investigation and angiogenesis on every stage elucidate role of redox buffering for the complete wound healing process.

A rare case of full recovery following delayed presentation of paraplegia secondary to thoracic epidural abscess: A case report and review of the literature.

Background: Timely diagnosis and prompt management of thoracic epidural abscesses are vital to preventing the onset of irreversible paralysis and death. Case Description: A 39-year-old female was managed initially for non-specific chest pain for 10 days (i.e., diagnosis of respiratory tract infection). After she developed paraplegia (0/5 motor function), a T10 sensory level, and acute urinary retention, a thoracic magnetic resonance with contrast revealed a T3-T7 spinal epidural abscess with cord compression. On review of her lab studies revealed a white blood cell count of 11.03 × 109/L and a C-reactive protein level of 122 mg/dL. Following a T3-T7 laminectomy with evacuation of an extradural empyema, she fully recovered. Conclusion: This case report emphasizes the need for early recognition, diagnosis, and treatment of thoracic epidural abscesses that are too often mis-diagnosed as respiratory infections.

Chitosan functionalized Mn3O4 nanoparticles counteracts ulcerative colitis in mice through modulation of cellular redox state.

Recent findings suggest a key role for reactive oxygen species (ROS) in the pathogenesis and progression of ulcerative colitis (UC). Several studies have also highlighted the efficacy of citrate functionalized Mn3O4 nanoparticles as redox medicine against a number of ROS-mediated disorders. Here we show that synthesized nanoparticles consisting of chitosan functionalized tri-manganese tetroxide (Mn3O4) can restore redox balance in a mouse model of UC induced by dextran sulfate sodium (DSS). Our in-vitro characterization of the developed nanoparticle confirms critical electronic transitions in the nanoparticle to be important for the redox buffering activity in the animal model. A careful administration of the developed nanoparticle not only reduces inflammatory markers in the animals, but also reduces the mortality rate from the induced disease. This study provides a proof of concept for the use of nanomaterial with synergistic anti-inflammatory and redox buffering capacity to prevent and treat ulcerative colitis.

Posterior cervical foraminotomy versus anterior cervical discectomy for Cervical Brachialgia: the FORVAD RCT.

Background: Posterior cervical foraminotomy and anterior cervical discectomy are routinely used operations to treat cervical brachialgia, although definitive evidence supporting superiority of either is lacking. Objective: The primary objective was to investigate whether or not posterior cervical foraminotomy is superior to anterior cervical discectomy in improving clinical outcome. Design: This was a Phase III, unblinded, prospective, United Kingdom multicentre, parallel-group, individually randomised controlled superiority trial comparing posterior cervical foraminotomy with anterior cervical discectomy. A rapid qualitative study was conducted during the close-down phase, involving remote semistructured interviews with trial participants and health-care professionals. Setting: National Health Service trusts. Participants: Patients with symptomatic unilateral cervical brachialgia for at least 6 weeks. Interventions: Participants were randomised to receive posterior cervical foraminotomy or anterior cervical discectomy. Allocation was not blinded to participants, medical staff or trial staff. Health-care use from providing the initial surgical intervention to hospital discharge was measured and valued using national cost data. Main outcome measures: The primary outcome measure was clinical outcome, as measured by patient-reported Neck Disability Index score 52 weeks post operation. Secondary outcome measures included complications, reoperations and restricted American Spinal Injury Association score over 6 weeks post operation, and patient-reported Eating Assessment Tool-10 items, Glasgow-Edinburgh Throat Scale, Voice Handicap Index-10 items, PainDETECT and Numerical Rating Scales for neck and upper-limb pain over 52 weeks post operation. Results: The target recruitment was 252 participants. Owing to slow accrual, the trial closed after randomising 23 participants from 11 hospitals. The qualitative substudy found that there was support and enthusiasm for the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial and randomised clinical trials in this area. However, clinical equipoise appears to have been an issue for sites and individual surgeons. Randomisation on the day of surgery and processes for screening and approaching participants were also crucial factors in some centres. The median Neck Disability Index scores at baseline (pre surgery) and at 52 weeks was 44.0 (interquartile range 36.0-62.0 weeks) and 25.3 weeks (interquartile range 20.0-42.0 weeks), respectively, in the posterior cervical foraminotomy group (n = 14), and 35.6 weeks (interquartile range 34.0-44.0 weeks) and 45.0 weeks (interquartile range 20.0-57.0 weeks), respectively, in the anterior cervical discectomy group (n = 9). Scores appeared to reduce (i.e. improve) in the posterior cervical foraminotomy group, but not in the anterior cervical discectomy group. The median Eating Assessment Tool-10 items score for swallowing was higher (worse) after anterior cervical discectomy (13.5) than after posterior cervical foraminotomy (0) on day 1, but not at other time points, whereas the median Glasgow-Edinburgh Throat Scale score for globus was higher (worse) after anterior cervical discectomy (15, 7, 6, 6, 2, 2.5) than after posterior cervical foraminotomy (3, 0, 0, 0.5, 0, 0) at all postoperative time points. Five postoperative complications occurred within 6 weeks of surgery, all after anterior cervical discectomy. Neck pain was more severe on day 1 following posterior cervical foraminotomy (Numerical Rating Scale - Neck Pain score 8.5) than at the same time point after anterior cervical discectomy (Numerical Rating Scale - Neck Pain score 7.0). The median health-care costs of providing initial surgical intervention were £2610 for posterior cervical foraminotomy and £4411 for anterior cervical discectomy. Conclusions: The data suggest that posterior cervical foraminotomy is associated with better outcomes, fewer complications and lower costs, but the trial recruited slowly and closed early. Consequently, the trial is underpowered and definitive conclusions cannot be drawn. Recruitment was impaired by lack of individual equipoise and by concern about randomising on the day of surgery. A large prospective multicentre trial comparing anterior cervical discectomy and posterior cervical foraminotomy in the treatment of cervical brachialgia is still required. Trial registration: This trial is registered as ISRCTN10133661. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 21. See the NIHR Journals Library website for further project information.

Cervical brachialgia is pain that starts in the neck and passes down into the arm. Although most people with cervical brachialgia recover quickly, in some patients pain persists, and in 15% of patients pain is so severe that they are unable to work. In the posterior cervical FORaminotomy Versus Anterior cervical Discectomy in the treatment of cervical brachialgia trial, we investigated two neck surgeries used to treat this problem: posterior cervical foraminotomy (surgery from the back of the neck) and anterior cervical discectomy (surgery from the front of the neck). This trial aimed to find out if one of them is better than the other at relieving pain and more cost-effective for the National Health Service. We assessed patients' quality of life 1 year after their surgery and how their pain changed over the course of the year. We also measured the number of complications patients had in the first 6 weeks after their operation. Recruitment was slow and so the trial was stopped early, after only 23 patients from 11 hospitals had been randomly allocated to the two surgery groups. We had planned to recruit 252 participants to the trial; the number of participants we were able to recruit in practice was too small to enable us to determine which surgery is better at relieving pain. To find out why the trial had struggled to recruit, we asked hospital staff and participants about their experiences. We found that hospital staff sometimes struggled to organise everything needed to randomise patients on the day of surgery. Some staff also found it difficult to randomise patients as they had an opinion on which surgery they thought the patient should receive. The data collected in the trial will still be useful to help design future research. Finding out which surgery is better at relieving pain remains important, and the data we have collected will support answering this question in future.

A nano erythropoiesis stimulating agent for the treatment of anemia and associated disorders.

The usual treatment for anemia and especially for anemia of inflammation (also called anemia of chronic disease) is supportive care with the target of improving the lifestyle of the patients. There is no effective medication to date for proper management. As the inflammation, erythropoiesis, and oxidative stress are the major concerns in this case, it inspired us to use a nano-erythropoietin stimulating agent (nano-ESA) made up of a nano-complex of manganese and citrate (Mn-citrate nano-complex), which has been hypothesized to have excellent antioxidant and anti-inflammatory mechanisms. Single oral dose of the nano-ESA efficiently prevented the onset of anemia as well as led to recovery from anemia in our phenylhydrazine (PHz)-intoxicated C57BL/6J mice model of anemia without any toxicological side effects. These preliminary findings may pave the way for an affordable and safe clinical use of the nano-ESA as a rapid recovery medication of anemia, especially anemia of inflammation.

Freehand determination of the trajectory angle for cervical lateral mass screws: how accurate is it?

Different methods of lateral mass screw placement in the cervical spine have been described with separate trajectories for each technique in the sagittal and parasagittal planes. In the latter, plane 30° has been recommended in the modified Magerl's technique as the optimum angle to avoid injury to the vertebral artery and nerve root. The estimation of this angle remains arbitrary and very much operator dependant. The aim of this study was to assess how accurately the lateral trajectory angle of 30° is achieved by visual estimation amongst experienced surgeons in a tertiary spinal unit and to determine the likelihood of neurovascular injury during the procedure. We chose an anatomical 'sawbone' model of the cervical spine with simulated lordosis. The senior author marked the entry points. Five spinal consultants and five senior spinal fellows were asked to insert 1.6-mm K wires into the lateral masses of C3 to C6 bilaterally at 30° to the midsagittal plane using the marked entry points. The lateral angulation in the transverse plane was measured using a custom protractor and documented for each surgeon at each level and side. The mean and standard deviation (SD) of the data were obtained to determine the inter observer variability. Utilising this data, measurements were then made on a normal axial computerised tomography (CT) scan of the cervical spine of an anonymous patient to determine if there would have been any neurovascular compromise. Among the 10 surgeons, a total of 80 insertion angles were measured from C3 to C6 on either side. The overall mean angle of insertion was 25.15 (range 20.4-34.8). The overall SD was 4.78. Amongst the 80 measurements between the ten surgeons, two episodes of theoretical vertebral artery violation were observed when the angles were simulated on the CT scan. A moderate but notable variability in trajectory placement exists between surgeons during insertion of cervical lateral mass screws. Freehand estimation of 30° is not consistently achieved between surgeons and levels. In patients with gross degenerative or deformed cervical spine anatomy, this may increase the risk of neurovascular injury. The use of the ipsilateral lamina as an anatomical reference plane is supported.

Factors relating to working hours restriction that have impacted the professional identity of trainees in the last decade.

Ever-developing changes to the working hours of junior doctors by the European Working Time Directive, the junior doctor contract of 2019 and most recently the COVID-19 pandemic have impacted the professional identity of doctors. There has been little investigation into its influence on the multifaceted aspects of postgraduate medical training, which feeds into how trainees consider themselves professionally and the concept of professional identity or 'being a doctor'. A review of the medical, socio-political and educational literature reveals that the impact on the professional identity development of trainees is influenced by several perspectives from the trainee, trainer and the public. Gross reduction in working hours has no doubt decreased the raw volume of clinical experiences. However, to counteract this, smarter learning processes have evolved, including narrative reflection, supervised learning events, and a greater awareness of coaching and training among trainers.

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Ruminococcus gnavus.

Microorganisms present in the guts are the causative agents for various diseases in humans. More and more studies are correlating such diseases and the responsible microorganism. The Gram-positive bacterium Ruminococcus gnavus (R. gnavus) has been identified to be responsible for symptoms of Crohn's disease. R. gnavas produces a glucorhamnan polysaccharide and it is postulated that this polysaccharide induces inflammatory response through toll-like receptor 4 (TLR4). The current manuscript describes the chemical synthesis of the pentasaccharide repeating unit of the O-polysachharide from R. gnavus. The major challenge associated with this particular synthesis is the presence of two consecutive 1,2-cis glucose units. The target oligosaccharide is achieved through a linear strategy from commercially available sugars through rational protecting group manipulation. 1,2-cis glycosylation of glucose through remote participation of acyl group at the 6-O position is used successfully with excellent yield. In both cases, sole 1,2-cis products are obtained at -20 °C through the activation of thioglycosides.

Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington's Like Disorder in Preclinical Model.

The potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, it is shown that citrate functionalized manganese-based biocompatible nanoscale material (C-Mn3 O4 NP) efficiently mimics glutathione peroxidase (GPx) enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H2 O2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. The in vivo therapeutic efficacy of C-Mn3 O4 nanozyme is further established in a preclinical animal model of Huntington's disease (HD), a prevalent progressive neurodegenerative disorder, which has no effective medication to date. Management of HD in preclinical animal trial using a biocompatible (non-toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy.

Redox Buffering Capacity of Nanomaterials as an Index of ROS-Based Therapeutics and Toxicity: A Preclinical Animal Study.

Precise control of intracellular redox status, i.e., maintenance of the physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress), is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, and depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate-functionalized trimanganese tetroxide nanoparticles (C-Mn3O4 NPs) as a model nanosystem, we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in the animal model to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use.

Direct Lateral Minimally Invasive Approach for Excision of a L1/L2 Neurofibroma-A Technical Note and Literature Review.

A case of resection of a large dumbbell-shaped nerve sheath tumor at L1/L2 via a direct lateral minimally invasive approach is described. The tumor was removed via a lateral, subdiaphragmatic, rib-sparing, retropleural, retroperitoneal approach. The thoracolumbar junction can be challenging via the lateral approach and to the best of our knowledge this is the first report of excision of a paravertebral tumor via this approach. We believe this provided the benefits of direct operative trajectory and exposure, excellent tumor access, and avoided the need for facetectomy and extended spinal instrumentation across the thoracolumbar junction. Complete tumor excision was achieved with preserved motor function and improvement in radicular pain and sensory neurological deficit.